chr11-61781402-G-A

Variant names:

• chr11-61781402-G-A
• rs174532
• NM_001127392.3:c.2764+73G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001127392.3(MYRF):​c.2764+73G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.255 in 1,571,074 control chromosomes in the GnomAD database, including 58,104 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.20 (4099 hom., cov: 33)
  • Exomes 𝑓: 0.26 (54005 hom.)
• Consequence: MYRF NM_001127392.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.590
• Publications: 37 publications found

Genes affected

MYRF (HGNC:1181): (myelin regulatory factor) This gene encodes a transcription factor that is required for central nervous system myelination and may regulate oligodendrocyte differentiation. It is thought to act by increasing the expression of genes that effect myelin production but may also directly promote myelin gene expression. Loss of a similar gene in mouse models results in severe demyelination. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2014]

TMEM258 (HGNC:1164): (transmembrane protein 258) Involved in protein N-linked glycosylation. Located in endoplasmic reticulum. Part of oligosaccharyltransferase I complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 11-61781402-G-A is Benign according to our data. Variant chr11-61781402-G-A is described in ClinVar as Benign. ClinVar VariationId is 1257534.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.29 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYRF	NM_001127392.3	c.2764+73G>A		intron_variant	Intron 21 of 26	ENST00000278836.10	NP_001120864.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYRF	ENST00000278836.10	c.2764+73G>A		intron_variant	Intron 21 of 26	1	NM_001127392.3	ENSP00000278836.4

Frequencies

GnomAD3 genomes AF: 0.199 AC: 30325 AN: 152108 Hom.: 4099 Cov.: 33

Gnomad AFR AF: 0.0541

Gnomad AMI AF: 0.387

Gnomad AMR AF: 0.216

Gnomad ASJ AF: 0.401

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0453

Gnomad FIN AF: 0.213

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.294

Gnomad OTH AF: 0.227

GnomAD4 exome AF: 0.261 AC: 370919 AN: 1418848 Hom.: 54005 Cov.: 31 AF XY: 0.256 AC XY: 179717 AN XY: 702446

African (AFR) AF: 0.0466 AC: 1506 AN: 32298

American (AMR) AF: 0.146 AC: 5999 AN: 41158

Ashkenazi Jewish (ASJ) AF: 0.403 AC: 9659 AN: 23990

East Asian (EAS) AF: 0.000459 AC: 18 AN: 39178

South Asian (SAS) AF: 0.0554 AC: 4549 AN: 82144

European-Finnish (FIN) AF: 0.224 AC: 11087 AN: 49604

Middle Eastern (MID) AF: 0.342 AC: 1904 AN: 5564

European-Non Finnish (NFE) AF: 0.296 AC: 322091 AN: 1086484

Other (OTH) AF: 0.241 AC: 14106 AN: 58428

GnomAD4 genome AF: 0.199 AC: 30317 AN: 152226 Hom.: 4099 Cov.: 33 AF XY: 0.194 AC XY: 14419 AN XY: 74414

African (AFR) AF: 0.0540 AC: 2243 AN: 41566

American (AMR) AF: 0.216 AC: 3299 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.401 AC: 1391 AN: 3472

East Asian (EAS) AF: 0.00135 AC: 7 AN: 5170

South Asian (SAS) AF: 0.0453 AC: 219 AN: 4830

European-Finnish (FIN) AF: 0.213 AC: 2262 AN: 10600

Middle Eastern (MID) AF: 0.337 AC: 99 AN: 294

European-Non Finnish (NFE) AF: 0.294 AC: 19970 AN: 67984

Other (OTH) AF: 0.224 AC: 475 AN: 2116

Alfa AF: 0.275 Hom.: 10405

Bravo AF: 0.195

Asia WGS AF: 0.0400 AC: 143 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

May 13, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	13
DANN	Benign	0.62
PhyloP100		0.59
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs174532; hg19: chr11-61548874;